Ibrutinib, a Bruton’s tyrosine kinase inhibitor, is used as a first-line treatment for chronic lymphocytic leukaemia. However, its poor hydrophobicity, small particle size and unfavourable drug responses from drug deposition in normal cells, restrict its use in treatment. Limitation can be overcome by encapsulation of ibrutinib in hyaluronic acid-conjugated PCL-Pluronic F68 nanoparticles, which is a hotspot in the field of biological therapy to treat human cancer. Polymeric nanoparticles containing Ibrutinib were synthesized using the solvent evaporation technique. FTIR and NMR Spectroscopy were used for the structural confirmation. Science-based innovation in the formulation was disclosed by the design matrix produced by Design Expert software and visually presented using a contour plot. It was discovered that polymeric nanoparticles particle sizes were between 39.47 to 128.6 nm, and had a zeta potential with −16.98 mv, negatively charged surface charge which help to remain monodispersed solution. The drug loading and entrapment efficacy were determined to be 16% and 83.15%, respectively, with 4 days of sustained drug release at the physiological pH. Conclusively, polymeric nanoparticles would serve as a platform for the transport of a targeted anticancer drug for the treatment of chronic lymphocytic leukaemia.